Spinal cord injury (SCI) affects approximately 10,000 individuals in the United States every year. SCI occurs most commonly in young adults, leaving them seriously disabled for the remainder of their lives. Apart from paralysis, patients of SCI suffer from additional disabilities including bladder, bowel and sexual dysfunction, and neuropathic pain syndromes. Several potentially useful therapeutic strategies have emerged over the last decade including the use of scaffolds and bridges, delivery of neurotrophic factors, other therapeutic peptides and use of stem cells to promote neuronal regeneration and functional recovery. However, none of the current strategies have shown enough effect to move to clinical trials and no major efforts have been undertaken to test a combination of these strategies, which can potentially be synergistic, and lead to greater therapeutic effect. Therefore, a need exists to develop a multifunctional construct which can integrate multiple, promising therapeutic strategies. This project brings together the disciplines of biomaterial engineering, neurobiology, basic neuroscience and neurosurgery in an attempt to develop a multi-disciplinary solution to the complex problem of spinal cord injury. We believe that the proposed system holds a number of benefits over previously described hydrogels, cellular and neurotrophin delivery systems in the CNS. Notably, the hydrogel is injectable and its properties can be readily tuned to match the compliance of host tissues, deliver therapeutic factors at tailored rates, and deliver cells to the injury site. In this case, we are delivering neural stem cells (NPC) to the site of spinal cord injury (SCI). These cells have been shown to survive and differentiate into neurons and glia and the hydrogel matrix can act as a scaffold that will include growth factors to further survival and differentiation of NPCs. We hypothesize that localized, sustained, simultaneous delivery of multiple therapeutic proteins into the CNS along with an injectable polymeric-cellular scaffold creates a synergistic effect by synchronously modulating the injured environment and activating different signaling pathways. By engineering this injectable hydrogel and cellular based scaffold to mimic the host tissues we can create a novel platform technology with applications in treatment of SCI and other tissue engineering applications. All the design parameters will be tested and validated using in-vitro bioassays and in-vivo experiments using rodent models of spinal cord injury.PUBLIC HEALTH RELEVANCE: Spinal cord injury (SCI) affects approximately 10,000 individuals in the United States every year. SCI occurs most commonly in young adults, leaving them seriously disabled for the remainder of their lives. We propose to develop a novel, injectable scaffold containing neural precursor cells and neurotrophic factors and hypothesize that localized, sustained, simultaneous delivery of multiple therapeutic proteins into the CNS along with an injectable polymeric-cellular scaffold creates a synergistic effect by synchronously modulating the injured environment and activating different signaling pathways. [unreadable] [unreadable]